By Professor Juan Tamargo, Madrid, Spain
The European Medicines Agency (EMA) has approved ivabradine for the treatment of chronic heart failure. This drug was licensed for stable angina since 2006. The EMA indicated that ivabradine it is suitable for patients with chronic heart failure: a) with symptoms (NYHA II-IV), b) involving systolic dysfunction and c) a regular rhythm and a heart rate of 75 beats a minute or more.
This new application is based on the results of the SHIFT study enrolling 6,558 patients with moderate to severe heart failure associated with left ventricular systolic dysfunction and resting heart rate of 70 bpm or higher, on optimum background therapy for at least 4 weeks.
Over a median follow-up period of 22.9 months, there were significantly fewer primary outcome events (composite of cardiovascular death or hospital admission for worsening heart failure) in the ivabradine group compared to the placebo group: 793 (24%) vs. 937 (29%) giving a hazard ratio (HR) of 0.82 (95% CI 0.75 to 0.90, p<0.0001). The majority of outcome events were admissions for worsening heart failure (21% for placebo vs. 16% for ivabradine; HR 0.74; 95% CI, 0.66 to 0.83; p<0.0001); there was also a significant reduction in deaths due to heart failure (5% vs. 3% respectively; HR 0.74; 95% CI, 0.58 to 0.94; p=0.014).
However, no differences in all-cause deaths (17% vs. 17%) and all cardiovascular deaths (15% vs. 14%) were observed. A secondary analysis published separately found that placebo-group patients in the highest quintile (≥87 bpm) were at a higher rate of an outcome event than those in the lowest quintile (70 to 72 bpm; HR 2.34, 95% CI 1.84 to 2.98, p<0.0001). The analysis of the ivabradine group found that those with a heart rate below 60 bpm at 4 weeks had a lower risk of outcome events than those with higher rates.
Therefore, it was concluded that in patients with moderate to severe chronic heart failure, ivabradine reduced the risk of hospitalisation for heart failure and death due to heart failure when added to standard optimum baseline treatment.